Shastry Surabhi, Hu Junkai, Ying Mingyao, Mao Xiaobo
Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Pharmaceutics. 2023 Nov 22;15(12):2656. doi: 10.3390/pharmaceutics15122656.
Parkinson's Disease (PD) is a neurodegenerative disease characterized by the progressive loss of dopaminergic neurons of the substantia nigra pars compacta with a reduction in dopamine concentration in the striatum. It is a substantial loss of dopaminergic neurons that is responsible for the classic triad of PD symptoms, i.e., resting tremor, muscular rigidity, and bradykinesia. Several current therapies for PD may only offer symptomatic relief and do not address the underlying neurodegeneration of PD. The recent developments in cellular reprogramming have enabled the development of previously unachievable cell therapies and patient-specific modeling of PD through Induced Pluripotent Stem Cells (iPSCs). iPSCs possess the inherent capacity for pluripotency, allowing for their directed differentiation into diverse cell lineages, such as dopaminergic neurons, thus offering a promising avenue for addressing the issue of neurodegeneration within the context of PD. This narrative review provides a comprehensive overview of the effects of dopamine on PD patients, illustrates the versatility of iPSCs and their regenerative abilities, and examines the benefits of using iPSC treatment for PD as opposed to current therapeutic measures. In means of providing a treatment approach that reinforces the long-term survival of the transplanted neurons, the review covers three supplementary avenues to reinforce the potential of iPSCs.
帕金森病(PD)是一种神经退行性疾病,其特征是黑质致密部多巴胺能神经元逐渐丧失,纹状体内多巴胺浓度降低。多巴胺能神经元的大量丧失导致了帕金森病经典的三联征症状,即静止性震颤、肌肉僵硬和运动迟缓。目前针对帕金森病的几种疗法可能只能缓解症状,无法解决帕金森病潜在的神经退行性变问题。细胞重编程技术的最新进展使得通过诱导多能干细胞(iPSC)开发以前无法实现的细胞疗法和帕金森病患者特异性模型成为可能。诱导多能干细胞具有多能性的内在能力,能够定向分化为多种细胞谱系,如多巴胺能神经元,从而为解决帕金森病背景下的神经退行性变问题提供了一条有前景的途径。这篇叙述性综述全面概述了多巴胺对帕金森病患者的影响,阐述了诱导多能干细胞的多功能性及其再生能力,并探讨了与当前治疗措施相比,使用诱导多能干细胞治疗帕金森病的益处。为了提供一种能够增强移植神经元长期存活的治疗方法,该综述涵盖了三种补充途径以增强诱导多能干细胞的潜力。